title: Cytotoxic necrotizing factor-Y boosts Yersinia effector translocation by activating Rac protein.
abstract: Pathogenic Yersinia spp. translocate the effectors YopT, YopE, and YopO/YpkA into target cells to inactivate Rho family GTP-binding proteins and block immune responses. Some Yersinia spp. also secrete the Rho protein activator cytotoxic necrotizing factor-Y (CNF-Y), but it has been unclear how the bacteria may benefit from Rho protein activation. We show here that CNF-Y increases Yop translocation in Yersinia enterocolitica-infected cells up to 5-fold. CNF-Y strongly activated RhoA and also delayed in time Rac1 and Cdc42, but when individually expressed, constitutively active mutants of Rac1, but not of RhoA, increased Yop translocation. Consistently, knock-out or knockdown of Rac1 but not of RhoA, -B, or -C inhibited Yersinia effector translocation in CNF-Y-treated and control cells. Activation or knockdown of Cdc42 also affected Yop translocation but much less efficiently than Rac. The increase in Yop translocation induced by CNF-Y was essentially independent of the presence of YopE, YopT, or YopO in the infecting Yersinia strain, indicating that none of the Yops reported to inhibit translocation could reverse the CNF-Y effect. In summary, the CNF-Y activity of Yersinia strongly enhances Yop translocation through activation of Rac.
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Wolters
authors.forename: Erin C
authors.initials: EC
authors.lastname: Boyle
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lardong
authors.forename: Konrad
authors.initials: K
authors.lastname: Trülzsch
authors.forename: Anika
authors.initials: A
authors.lastname: Steffen
authors.forename: Klemens
authors.initials: K
authors.lastname: Rottner
authors.forename: Klaus
authors.initials: K
authors.lastname: Ruckdeschel
authors.forename: Martin
authors.initials: M
authors.lastname: Aepfelbacher
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D015009:Yersinia Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015008:Yersinia enterocolitica / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D009479:Neuropeptides; C107953:RAC1 protein, human; C484602:Rac1 protein, mouse; C066737:RHOA protein, human; C066690:RHOC protein, human; C526380:RhoA protein, mouse; C512911:Rhoc protein, mouse; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein
keywords: CNF-Y; Cdc42; Cytotoxic Necrotizing Factor-Y; Rac; Rho; Rho GTPases; Toxins; Type III Secretion System; Yersinia enterocolitica